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Type 2 Diabetes MellitusNCT00865124

Role of Mineralocorticoid Receptor in Diabetic Cardiovascular Disease

A study testing Spironolactone and Hydrochlorothiazide + potassium in people with Type 2 Diabetes Mellitus and Vascular Disease, run by Brigham and Women's Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Aldosterone is a significant mediator of cardiovascular injury associated with heart failure and the cardiovascular benefits of mineralocorticoid receptor blockade are additive to those of angiotensin converting enzyme inhibitors or angiotensin II (ANGII) receptor blockers. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Type 2 Diabetes Mellitus, Vascular Disease
What is being tested?
Spironolactone and Hydrochlorothiazide + potassium
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
69 participants
Where
1 siteUnited States
Study dates
Sep 2008to May 2014
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • age 18-70 years
  • type 2 diabetes mellitus
  • with or without hypertension

Who cannot join

  • ischemic changes on resting electrocardiogram,
  • clinical evidence of heart disease (angina, heart failure, unstable angina),cerebrovascular or peripheral vascular disease,
  • significant cardiac arrhythmias,
  • aortic stenosis,
  • 2nd or 3rd degree atrio-ventricular block, sinus node disease, or symptomatic bradycardia,
  • bronchospastic lung disease with active wheezing,
Show all 23Show fewer
  • known hypersensitivity to adenosine,
  • hemoglobin A1C (HbA1c) > 8.5%, *
  • gout (If not already taking HCTZ),
  • the use of Rosiglitazone,**
  • estimated glomerular filtration rate (eGFR) < 60 ml/min,
  • serum potassium > 5.0 mmol/L,
  • use of potassium-sparing diuretics,**
  • current smoker,*
  • pregnancy,
  • renal disease not related to diabetes mellitus,
  • uncontrolled hypertension, systolic blood pressure (BP) >160 mm Hg and diastolic BP >100 mm Hg,*
  • use of cyclic hormone replacement therapy
  • past intolerance of angiotensin-converting enzyme (ACE) inhibitor therapy
  • other major medical illnesses. Participants with evidence of a previous myocardial infarction on the first adenosine-stimulated positron emission tomography (PET) study will be withdrawn from the study.
  • Screening systolic blood pressure < 105 mm Hg off of anti-hypertensive medications
  • Participants can enroll in study and proceed with in-patient evaluations if during the run-in period adjustments of medications, diet and habits lead to improved glucose control [equivalent to HbA1c <8.5%, controlled hypertension and cessation of smoking.
  • Participants who are currently taking these medications will not qualify for a screening visit. If medications were recently stopped by the participant's physician, he or she may be screened but the baseline assessment protocol must occur 3 months after stopping.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

Other trials in United States

About this study

Aldosterone is a significant mediator of cardiovascular injury associated with heart failure and the cardiovascular benefits of mineralocorticoid receptor blockade are additive to those of angiotensin converting enzyme inhibitors or angiotensin II (ANGII) receptor blockers. This study will test the hypothesis that mineralocorticoid receptor (MR) antagonists exert beneficial cardiovascular effects, specifically by decreasing vascular injury and improving vascular function. A randomized, double-blind study will be conducted, in which participants with Type 2 Diabetes Mellitus will undergo a series of assessments to test heart, blood vessel, and kidney function at baseline, and after 2 and 6 months of treatment with one of the following drugs:

  1. spironolactone
  2. hydrochlorothiazide (HCTZ) plus potassium
  3. placebo

In the event of insufficient funds, randomization to the placebo arm will be stopped and primary assessment of outcomes will occur at baseline and after 6 months of treatment.

Being tested
Spironolactone, Hydrochlorothiazide + potassium, Placebo
Medical subject headings
Diabetes Mellitus, Type 2, Vascular Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SpironolactoneDrug

    25 mg capsule daily for 6 months

  • Hydrochlorothiazide + potassiumDrug

    hydrochlorothiazide (HCTZ) + potassium, 12.5 mg/10 milliequivalents (mEq) capsule daily

  • PlaceboOther

    Placebo capsule daily

Study groups in NCT00865124
Study groupRoleWhat they receive
Spironolactone (mineralocorticoid receptor [MR] blockade)ExperimentalNot described
Receives: Drug: Spironolactone
Hydrochlorothiazide + potassiumActive comparatorNot described
Receives: Drug: Hydrochlorothiazide + potassium
Placebo capsulePlacebo comparatorNot described
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Coronary Flow Reserve From Baseline to 6 Months

    Coronary flow reserve (CFR), or myocardial perfusion reserve, was assessed via cardiac positron emission tomography (PET). CFR is the ratio of adenosine-stimulated blood flow through myocardium to resting blood flow through myocardium. An improvement in coronary flow reserve is beneficial.

    Measured: Baseline and six months

Secondary outcomes (3)

  1. Change in Mitral Annulus Velocities on Tissue Doppler (Delta E/e' Ratio), a Measure of Diastolic Function

    Diastolic function was assessed via tissue doppler imaging (TDI) by echocardiography to determine left ventricular diastolic function before and after 6 months of treatment.

    Measured: Baseline and six months

  2. Mitral Annulus Velocities on Tissue Doppler (Delta E/e' Ratio), a Measure of Diastolic Function (With Angiotensin II)

    Diastolic function was assessed via tissue doppler imaging (TDI) by echocardiography to determine left ventricular diastolic function before and after 6 months of treatment; and in response to acute administration (3 nanograms/kg/min for 60 min) of the vasoactive agent, Angiotensin II.

    Measured: Baseline and six months

  3. Change in Renal Plasma Flow

    Renal vasculature was assessed by examining renal plasma flow, or para-aminohippurate (PAH) clearance, basally and in response to acute administration (3 nanograms/kg/min for 60 min) of the vasoactive agent, Angiotensin II.

    Measured: Baseline and six months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Mar 2009 (estimated)
  2. Study startSep 2008
  3. Primary completionAug 2013
  4. Study completionMay 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
69 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00865124
Sponsor's protocol ID
2007-P-000564
Other IDs
1R01HL087060-01A2
Status last verified
May 2017
First submitted
17 Mar 2009
Last updated
14 Jun 2017
Data monitoring committee
Yes

Publications

  • Haas AV, Rosner BA, Kwong RY, Rao AD, Garg R, Di Carli MF, Adler GK. Sex Differences in Coronary Microvascular Function in Individuals With Type 2 Diabetes. Diabetes. 2019 Mar;68(3):631-636. doi: 10.2337/db18-0650. Epub 2018 Nov 8.

    PubMed 30409780

  • Garg R, Rao AD, Baimas-George M, Hurwitz S, Foster C, Shah RV, Jerosch-Herold M, Kwong RY, Di Carli MF, Adler GK. Mineralocorticoid receptor blockade improves coronary microvascular function in individuals with type 2 diabetes. Diabetes. 2015 Jan;64(1):236-42. doi: 10.2337/db14-0670. Epub 2014 Aug 14.

    PubMed 25125488

Questions about this trial

What is this clinical trial studying?

A study testing Spironolactone and Hydrochlorothiazide + potassium in people with Type 2 Diabetes Mellitus and Vascular Disease, run by Brigham and Women's Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Coronary Flow Reserve From Baseline to 6 Months (time frame: Baseline and six months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00865124, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2017.

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